MICROBICIDAL AGENTS FOR HSV AND HIV-1--IN VITRO STUDIES

  • Herold, Betsy (PI)
  • Zaneveld, Lourens J. (PI)
  • Reising, Shirley Floyd (PI)
  • Spear, Patricia (PI)
  • Cooper, Morris (PI)
  • Stanberry, Lawrence (PI)
  • Zaneveld, Lourens J. (PI)
  • Reising, Shirley Floyd (PI)
  • Spear, Patricia (PI)
  • Cooper, Morris (PI)
  • Stanberry, Lawrence (PI)

Project: Research project

Project Details

Description

In this project, investigators from three sites in Chicago (Northwestern
University Medical School, University of Chicago Medical Center, and Rush-
Presbyterian-St. Luke's Medical Center) propose collaborative studies on
herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and human
immunodeficiency virus type 1 (HIV-1). One of the principal objectives of
this project is to identify antimicrobial agents that are effective in
preventing the infection of cultured cells by HSV-1, HSV-2 and HIV-1. The
cultured cell types will include those used routinely for in vitro
infectivity studies (HeLa cells for HSV and peripheral blood mononuclear
cells [PMNC] for HIV) as well as primary human cells cultured from the
female preproductive tract (principally cells obtained from the epithelium
of the cervix and adjacent vagina). The candidate antimicrobial agents
include sulfated polysaccharides selected for their potential to block the
binding of HSV and HIV-1 to cells and surface-active agents that are
expected to damage the envelopes of these viruses. A second important
objective of project 1 is to explore the cellular and viral determinants
for HSV and HIV-1 infection of primary human cells cultured from the female
reproductive tract, in order to assess whether the requirements are similar
to or different from those already established for permanent cell lines.
The specific aims are to (i) evaluate the efficacy and cytotoxicity of
potential topical microbicides in prevention of HSV-1, HSV-2 and HIV-1
infection of cultured cell types as outlined above; (ii) generate mutants
of pathogenic strains of HSV-1 and HSV-2 to obtain strains that are
impaired in ability to affect HeLa cells and other permanent cell lines;
and (iii) evaluate HSV parental strains and mutants and selected strains of
HIV-1 for their ability to infect primary human cells cultured from the
female reproductive tract, before and after treatments of athe cells that
are predicted to alter or mask cell receptors for the viruses. The HSV
mutants generated in this project will also be used in project 3 for
studies designed to define determinants of pathogenicity in the guinea pig
model of genital infection. From the information obtained in all three
projects, we will identify the microbicide that are most effective in
protecting cells and tissues of the female reproductive tract against
infection by HIV-1, HSV and chlamydia and will define some of the key
cellular and viral determinants for establishment of infection in these
cells and tissues.
StatusFinished
Effective start/end date1/1/017/31/05

ASJC

  • Infectious Diseases
  • Toxicology
  • Microbiology
  • Immunology
  • Medicine(all)
  • Virology
  • Cell Biology

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